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How does alcohol cause cancer?

A new study looking at blood stem cells uncovered fresh details surrounding the mechanisms by which alcohol raises the risk of developing cancer.

A new study unearths the details of cancer's relationship with alcohol.

Alcohol is known to raise the risk of no fewer than seven types of cancer. These are mouth, upper throat (pharynx), voice box (laryngeal), esophageal, breast, liver, and bowel cancer.

Though the links are established, exactly how alcohol works to induce malignancy is not as well-understood. Several mechanisms are thought to be at work.

Most previous studies have only examined cells in the laboratory, looking at changes in them after exposure to alcohol (ethanol).

Recently, researchers from MRC Laboratory of Molecular Biology in Cambridge, United Kingdom, set out to gain a clearer picture of the alcohol-cancer relationship using whole animals.

Their study, which was funded by Cancer Research U.K., is published this week in the journal Nature.

Acetaldehyde and blood stem cells

The team fed diluted ethanol to mice and then used chromosome analysis and DNA sequencing to measure any damage caused by acetaldehyde, a chemical produced when alcohol is processed. They focused their attention on a specific cell type: blood stem cells.

Blood stem cells, found in blood and bone marrow, are immature blood cells that can develop into any type of blood cell, including white blood cells, platelets, and red blood cells. It is important to understand how alcohol damages these cells, as faulty stem cells are known to cause cancer.

As alcohol is broken down in the gut, bacteria convert it into large quantities of acetaldehyde, a chemical that has previously been shown to cause cancer in animals.

Following the analysis, the researchers found that acetaldehyde could, in fact, damage and break DNA within blood stem cells. Chromosomes became rearranged, and the DNA sequence was permanently changed in stem cells.

Lead study author Prof. Ketan Patel says, "Some cancers develop due to DNA damage in stem cells. While some damage occurs by chance, our findings suggest that drinking alcohol can increase the risk of this damage."

Self-defense mechanisms

Alongside new insights into the damage that ethanol causes to stem cells, the scientists uncovered new information about the protective mechanisms employed by our bodies in response to alcohol.

Enzymes called aldehyde dehydrogenases (ALDHs) form the first line of defense against alcohol-related damage. ALDHs break alcohol down into acetate, "which our cells can use as a source of energy."

Millions of people — many East Asians, for instance — have low levels of ALDH or faulty copies of the enzymes. This means that toxic acetaldehyde builds up in the body. These individuals will experience tell-tale flushed cheeks and potentially feel ill.

When the researchers investigated mice without ALDH, they found that alcohol caused four times as much damage to DNA when compared with mice that could produce ALDH.

Beyond ALDH, the body has a range of other secondary mechanisms that can repair various types of DNA damage. But these mechanisms do not always work; some people have mutations that render them ineffective.

"Our study highlights that not being able to process alcohol effectively can lead to an even higher risk of alcohol-related DNA damage and therefore certain cancers."

Prof. Ketan Patel

"But," he continues, "it's important to remember that alcohol clearance and DNA repair systems are not perfect and alcohol can still cause cancer in different ways, even in people whose defense mechanisms are intact."

Alcohol is known to give rise to cancer, and studies such as this help us to understand why and will, eventually, help to prevent or slow alcohol-related cancers.

As Prof. Linda Bauld, from Cancer Research U.K., says, "This thought-provoking research highlights the damage alcohol can do to our cells, costing some people more than just a hangover."

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